2-166085630-C-T

Position:

• chr2-166085630-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001165963.4(SCN1A):​c.-141-7829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,874 control chromosomes in the GnomAD database, including 3,554 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3554 hom., cov: 31)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

SCN1A (HGNC:10585): (sodium voltage-gated channel alpha subunit 1) Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]

SCN1A-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1A	NM_001165963.4	c.-141-7829G>A		intron_variant		ENST00000674923.1	NP_001159435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1A	ENST00000674923.1	c.-141-7829G>A		intron_variant			NM_001165963.4	ENSP00000501589.1
SCN1A	ENST00000303395.9	c.-141-7829G>A		intron_variant		5		ENSP00000303540.4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32456 AN: 151756 Hom.: 3556 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.214 AC: 32466 AN: 151874 Hom.: 3554 Cov.: 31 AF XY: 0.209 AC XY: 15490 AN XY: 74208

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.243

Alfa AF: 0.107 Hom.: 170

Bravo AF: 0.219

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.053
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11904006; hg19: chr2-166942140;